Spinocerebellar Ataxias in Brazil—Frequencies and Modulating Effects of Related Genes
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This study describes the frequency of spinocerebellar ataxias and of CAG repeats range in different geographical regions of Brazil, and explores the hypothetical role of normal CAG repeats at ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 genes on age at onset and on neurological findings. Patients with symptoms and family history compatible with a SCA were recruited in 11 cities of the country; clinical data and DNA samples were collected. Capillary electrophoresis was performed to detect CAG lengths at SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA12, SCA17, and DRPLA associated genes, and a repeat primed PCR was used to detect ATTCT expansions at SCA10 gene. Five hundred forty-four patients (359 families) were included. There were 214 SCA3/MJD families (59.6 %), 28 SCA2 (7.8 %), 20 SCA7 (5.6 %), 15 SCA1 (4.2 %), 12 SCA10 (3.3 %), 5 SCA6 (1.4 %), and 65 families without a molecular diagnosis (18.1 %). Divergent rates of SCA3/MJD, SCA2, and SCA7 were seen in regions with different ethnic backgrounds. 64.7 % of our SCA10 patients presented seizures. Among SCA2 patients, longer ATXN3 CAG alleles were associated with earlier ages at onset (p < 0.036, linear regression). A portrait of SCAs in Brazil was obtained, where variation in frequencies seemed to parallel ethnic differences. New potential interactions between some SCA-related genes were presented.
KeywordsSpinocerebellar ataxias SCA3/MJD SCA2 SCA7 SCA10 Modifier genes
We would like to thank the patients and their families for taking part in this study. We would also like to thank Thais Santa Rita for her technical assistance; Vanessa Erichsen Emmel and Alexis Trott for their contribution in early stages of this project; and Pedro Braga-Neto, Isabel Cristina Neves de Souza, and Raimunda Helena Feio for their contribution in recruiting some patients. This study was supported by FAPERGS, CNPq, CAPES, INAGEMP, and FIPE-HCPA. Castilhos RM was supported by INAGEMP. Furtado GV was supported by CAPES. Gheno TC, Russo A, Saraiva-Pereira ML, and Jardim LB were supported by CNPq.
Conflict of Interest
The authors state that there is no potential conflict of interest
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